This research is primarily aimed at assessing comparatively the potential carcinogenic potency of tritiated water following continuous low level exposure of C57 Black/6 M mice from conception, birth or weaning for the rest of the lifespan, versus administration of tritiated thymidine, uridine or leucine at birth, in relation with specific patterns and sites of incorporation, as observed in our previous research. The completed carcinogenic studies will require observation of 4,363 mice during their entire lifespan. Microscopic pathology on all gross abnormalities and on most organs and tissues is aimed at providing an extensive definition of the basic tumor spectrum in controls and of the modulated spectra in experimental mice. Actuarial analysis based on age specific mortality and tumor incidence rates observed to date revealed: (1) an extremely high incidence of naturally occurring tumors in control mice and (2) a dose-dependent induction of adenocarcinomas of the ileum in mice exposed to tritiated thymidine at birth. In an attempt to evaluate the potential cumulative genetic injury of tritium, three sublines have been propagated from three sibling couples whose male parent was at weaning time, either injected with tritiated thymidine or exposed for 35 days to tritiated drinking water or exposed to natural water. At the present time, 14 successive generations have been produced. It is planned to carry the experiment to the 20th generation. An increasing reduction of offspring through successive generations has been consistently observed in sublines exposed to tritium. A significant increase in dominant lethal mutation was observed in the unexposed F2 offspring from the 9th generation in sublines exposed to tritium. The F1 offspring is currently under observation for tumor incidence in an attempt to detect any possibly shift from the basic tumor spectrum. A duplicate assessment of reproductive fitness and dominant lethal mutations is planned at the 20th generation, using part of the F2 offspring. The F1 and the unused F2 offspring will be assigned to parallel long-term studies investigating any possible shift from the basic tumor spectrum.